[en] Cadmium caused a spike in cytoplasmic free [Ca⁺] ([Ca⁺]_i) similarly to bradykinin in cultured human skin fibroblasts. Cadmium increased [Ca²⁺]_i in the presence or absence of external Ca²⁺. After bradykinin produced a spike in [Ca²⁺]_i, the addition of cadmium had no effect on [Ca²⁺]_i indicating that cadmium and bradykinin release Ca²⁺ from the same intracellular pool. Cadmium triggered a concentration-dependent increase in ⁴⁵Ca²⁺ efflux. Half-maximal stimulation of efflux occurred at 0.1 μM cadmium. Certain other metals also stimulated ⁴⁵Ca²⁺ efflux. The potency order of the metals was Cd²⁺ > Co²⁺ > Ni²⁺ > Fe²⁺ > Mn²⁺. Zn²⁺ competitively inhibited Cd-evoked ⁴⁵Ca²⁺ efflux but had no effect on bradykinin-evoked efflux. Cadmium also decreased total cell Ca²⁺ by 50-60% within 2 min similarly to bradykinin. Decreasing external Na⁺ from 120 mM to 3 mM caused a spike in [Ca²⁺]_i, an 8-fold increase in ⁴⁵Ca²⁺ efflux, and rapidly decreased total cell Ca²⁺ by 40% similarly to cadmium and bradykinin. Decreasing external pH also increased [Ca²⁺]_i, stimulated ⁴⁵Ca²⁺ efflux, and decreased total cell Ca²⁺. The three unusual stimuli (cadmium, decreasing external Na⁺, and decreasing external pH) trigger rapid increases in [³H] inositol 1,4,5-trisphosphate (IP₃), which indicates that IP₃ is the intracellular messenger for release of stored Ca²⁺ by these three unusual stimuli. A single receptor appears to mediate the Ca²⁺ mobilizing response to all three stimuli

[en] Angiotensin II (ANG) stimulates the hydrolysis of phosphatidylinositol bisphosphate with the consequent formation of inositol trisphosphate and diacylglycerol in cultured smooth muscle cells derived from rat aorta. They have observed the effects of ANG on protein and DNA synthesis by measuring the incorporation of ³H-leucine and ³H-thymidine, respectively, into acid-precipitable material. Aortic muscle cells were grown to confluence in medium containing 10% fetal bovine serum (FBS) and incubated for 24 hours in serum-free medium to arrest growth. Then fresh serum-free medium was added with the following additions: ANG (100 nM), insulin (2 μg/ml), or 10% FBS. After an additional 24 hours the cells were pulse labeled for 30 min with either ³H-leucine or ³H-thymidine. FBS increased ³H-leucine incorporation by -2.5 fold and ³H-thymidine incorporation by 7-10 fold. ANG or insulin increased ³H-leucine incorporation by 40-50%, and the combination of ANG and insulin was nearly as effective as 10% FBS. ANG stimulated ³H-thymidine incorporation by -2.5 fold. Insulin, which was less effective than ANG, increased ³H-thymidine incorporation by about 50%. ANG and insulin added together synergistically increased ³H-thymidine incorporation by 5-6 fold. An ANG antagonist, Sarl,leu8-ANG, at 2 μM markedly decreased ³H-thymidine incorporation in the presence of ANG and insulin

[en] Removing extracellular Na+ (Na+o) evoked a large increase in cytosolic free Ca2+ concentration ([Ca2+]i in human skin fibroblasts. Decreasing [Na+]o from 120 to 14 mM caused the half-maximal peak increase in [Ca2+]i. Removing Na+o strongly stimulated ⁴⁵Ca2+ efflux and decreased total cell Ca2+ by about 40%. Bradykinin caused changes in [Ca2+]i, total Ca2+, and ⁴⁵Ca2+ fluxes similar to those evoked by removing Na+o. Prior stimulation of the cells with bradykinin prevented Na+o removal from increasing [Ca2+]i and vice versa. Na+o removal rapidly increased [³H]inositol polyphosphate production. Loading the cells with Na+ had no effect on the increase in ⁴⁵Ca2+ efflux produced by Na+o removal. Therefore, decreasing [Na+]o probably stimulates a receptor(s) which is sensitive to extracellular, not intracellular, Na+. Removing Na+o also mobilized intracellular Ca2+ in smooth muscle and endothelial cells cultured from human umbilical and dog coronary arteries, respectively

[en] Cadmium (1 μM) or decreasing external pH (pH_o) or Na concentration (Na_o) transiently increased cytoplasmic free Ca (Ca_i) by ∼5-fold as measured with fura-2 in endothelial cells grown on cover glasses. Cd or pH_o=6 evoked similar peak Ca_i increases in the presence or absence of external Ca indicating that they trigger the release of stored Ca. Cd or 4 mM Na_o, but not pH_o 6, caused sustained Ca_i increases. The sustained phase of the Ca_i response to Cd required external Ca. Decreasing intracellular pH with propionate had no effect on Ca_i. Cd and some other divalent metals also stimulated 45Ca efflux. The potency order of the metals that stimulated efflux was Cd > Co > Ni > Fe(II) > Mn. Cd apparently acts at an extracellular site because loading the cells with a heavy metal chelator (TPEN) only slightly affected Cd- or ATP-stimulated 45Ca efflux. Addition of Zn or Cu(II) to the assay solution prevented the stimulation of efflux by Cd and had no effect on ATP-evoked efflux. Decreasing Na_o stimulated 45Ca efflux ∼4-fold and slightly increased 45Ca influx. Decreasing Na_o to 27 mM or pH_o to 6.4 half-maximally increased 45Ca efflux. The stimulation of efflux was independent of external Ca or the osmotic Na substitute. The release of stored Ca, not Ca influx via Na-Ca exchange, causes the increase in Ca_i and 45Ca efflux evoked by decreasing Na_o. Incubating the cells with Zn prior to assaying efflux in the absence of Zn strongly inhibited the stimulation of 45Ca efflux by Cd, pH_o 6, and the Na_o removal. Desensitization by Zn had no effect on ATP-stimulated efflux. These finding support the hypothesis proposed previously that the trace metals or decreasing external Na or pH release stored Ca by stimulating the same cell surface receptor